Jane L. Hoover-Plow, Ph.D. Associate Staff Department of Cardiovascular Medicine J.J. Jacobs Center for Thrombosis and Vascular Biology Department of Molecular Cardiology, NB50 Lerner Research Institute 9500 Euclid Avenue Cleveland, OH 44195 Telephone: (216) 445-8207 FAX: (216) 445-8204 email: hooverj@ccf.org

Area of General Research Interest:

Mechanisms of plasminogen dependent cell migration in inflammation and stem cell mobilization; genetic determinants of atherothrombosis.

Current Program:

• The plasminogen dependent proteolysis in leukocyte migration in inflammation and stem cell mobilization
• Plasminogen and lipoprotein(a) interactions in the development of thrombosis
• Genetic determinants of thrombosis
• Role of extracellular matrix Emilin proteins in thrombosis

Investigators:

• Gong, Yanqing, PhD, Research Associate
• Grondolsky, Jessica, Husbandry Technician
• Huang, Menggui, Ph.D., Postdoctoral Fellow
• Zhao, Nan, Graduate Student

Collaborators:

• Giorgio M. Bressan, MD, Padua University, Italy
• Joseph Nadeau, PhD, Seattle, Washington
• Edward F. Plow, PhD, Cleveland Clinic

Brief Description:

Many studies document the association of inflammatory and hemostatic markers with cardiovascular disease (CVD), suggesting that inflammation and thrombosis are critical factors in its initiation/progression.

Studies of mice in which genes for plasminogen (Plg) and other Plg system components have been inactivated implicate Plg in several physiological and pathological processes unrelated to clot lysis; of particular relevance to the pathogenesis of CVD is cell migration.

Our data show that Plg exerts a profound effect on inflammatory cell mobilization, and we are evaluating the inflammatory response in aortic aneursyms, stem cell mobilization and extracellular matrix (ECM) remodeling, key events in the development and recovery phases of CVD. Apo(a), structurally similar to Plg, when overexpressed in mice exhibits both Plg-dependent and -independent effects in inflammatory and vascular injury models.

We have a longstanding collaboration with Joseph Nadeau, PhD, of Case Western Reserve University regarding the identification of genetic factors of thrombotic risk. We are investigating the Emilin1 and Emilin2, extracellular matrix proteins, as possible genetic modifiers.

Key References:

• Sa, Q, Hart E, Nadeau JH, Hoover-Plow J. Mouse chromosome 17 candidate modifier genes for thrombosis. Mamm Genome. 21:337-49, 2010. PMID: 20700597
• Hoover-Plow J, Hart E, Gong Y, Shchurin A, Schneeman T. A physiological function for apolipoprotein(a): A natural regulator of the inflammatory response. Exp Biol Med 234:28–34, 2009. PMID: 18997104
• Hoover-Plow JL, Gong Y, Shchurin A, Busuttil SJ, Schneeman TA, Hart E. Strain and model dependent differences in inflammatory cell recruitment in mice. Inflamm Res 57:457–463, 2008. PMID: 18827970
• Sa Q, Hart E, Hill AE, Nadeau JH, Hoover-Plow JL. Quantitative trait locus analysis for hemostasis and thrombosis. Mamm Genome 19:406–412, 2008. PMID: 18787898
• Gong Y, Hart E, Shchurin A, Hoover-Plow J. Inflammatory macrophage migration requires MMP-9 activation by plasminogen in mice. J Clin Invest 118:3012–3024, 2008. PMID: 18677407
• Hoover-Plow J, Shchurin A, Hart E, Sha J, Hill AE, Singer JB, Nadeau JH. BMC Blood Disord 6:6, 2006. PMID: 17022820
• Hoover-Plow J. Elusive proatherothrombotic role of Lp(a): A new direction? J Thromb Haemost 4:971–972, 2006. PMID: 16689744
• Sha J, McCullough B, Hart E, Nassir F, Davidson NO, Hoover-Plow J. Apo(a) promotes thrombosis in a vascular injury model by a mechanism independent of plasminogen. J Thromb Haemost 3:2281–2289, 2005. PMID: 16150044
• Plow EF, Hoover-Plow J. The functions of plasminogen in cardiovascular disease. Trends Cardiovasc Med 14:180–186, 2004. PMID: 15261889
• Hoover-Plow, J. Lessons learned from the plasminogen deficient mice. In: Plasminogen: Structure, Activation, and Regulation. (D.M. Waisman, ed.) Kluwer Academic/Plenum Publishers, New York, pp. 159–176, 2003.